The Neurobiology of Drug Addiction

6: Definition of tolerance

When drugs such as heroin are used repeatedly over time, tolerance may develop. Tolerance occurs when the person no longer responds to the drug in the way that person initially responded. Stated another way, it takes a higher dose of the drug to achieve the same level of response achieved initially. For example, in the case of heroin or morphine, tolerance develops rapidly to the analgesic effects of the drug. [The development of tolerance is not addiction, although many drugs that produce tolerance also have addictive potential.] Tolerance to drugs can be produced by several different mechanisms, but in the case of morphine or heroin, tolerance develops at the level of the cellular targets. For example, when morphine binds to opiate receptors, it triggers the inhibition of an enzyme (adenylate cyclase) that orchestrates several chemicals in the cell to maintain the firing of impulses. After repeated activation of the opiate receptor by morphine, the enzyme adapts so that the morphine can no longer cause changes in cell firing. Thus, the effect of a given dose of morphine or heroin is diminished.